Project Summary/Abstract Late-stage C?H functionalization of biologically active molecules is an emerging technology for the discovery of new and lifesaving drugs. The value of late-stage C?H functionalization to drug discovery is manifested in the ability to rapidly synthesize analogues of promising drug targets in order to enhance their bioactive properties. Site-selective C?H functionalization can be accomplished by exploiting the innate reactivity of different C?H bonds in a certain molecule, however, a more predictable and chemoselective approach to C?H functionalization is through the use of a directing group. In the past decade, several effective protocols for directed C?H oxidation have been developed, but, despite their immense potential as site-selective late-stage C?H functionalization strategies, the boundaries of these transformations have yet to be explored in a more complex molecule setting. The isoryanoids are a family of natural products with a unique 5-6-5 ring system and varying patterns of peripheral oxygenation, making them prime candidates on which to explore a directed C?H oxidation approach. Like the related ryanoids, which are known to bind with an extremely high affinity to ryanodine receptors, the isoryanoids exhibit high levels of insecticidal and antifeedant activity. Although their structural similarities to the ryanoids suggest that the isoryanoids may have further promising biological applications, additional bioactivity has yet to be investigated, perhaps due to their synthetic inaccessibility. The goal of the proposed research is to accomplish the first total synthesis of the isoryanoid, perseanol, which will utilize directed C?H oxidation methodology in order to evaluate its viability as a strategy for late-stage C?H functionalization in a complex molecule setting. Not only would the achievement of these aims mark an advance in the growing field of C?H functionalization, but it would also be a significant contribution in the area of drug discovery by identifying new methods for introducing late-stage structural modifications to bioactive molecules.